The long-term goal of this research program is to define the structure, metabolism, and function of proteoglycans as they occur in normal and diseased connective tissue. The research proposal emphasizes studies designed to elucidate the underlying biochemical processes associated with the endocytosis of lysosomal enzymes (testicular beta-galactosidase and liver beta-glucuronidase) and proteoglycans (chondroitin sulfate-keratan sulfate proteoglycan complex), and their packaging by normal and mutant cells. Attempts are being made to characterize the specific recognition marker signal contained in these compounds, and to characterize the specific receptor(s) contained on mammalian cell membranes. In addition, we are continuing studies concerned with the biosynthesis and degradation of keratan sulfate. These studies include: 1) examination of the possible participation of lipid-phospho-oligosaccharides in the biosynthesis of the carbohydrate chains, and 2) examination of glycosidases involved in the catabolism of keratan sulfate in mammalian tissues and cultured cells derived from connective tissue.